RESEARCH ARTICLE

Neurorehabilitation Therapy in Spinocerebellar Ataxia Type 2:

A 24-Week, Rater-Blinded, Randomized, Controlled Trial
Julio Cesar Rodrı́guez-Dı́az, BSc,1 Luis Vela
zquez-Pe rez, DSc,1,2,3* Roberto Rodrı́guez Labrada, PhD,1,2,3
l Aguilera Rodrı́guez, MD,1 Dalina Laffita Pe
Rau rez, BSc,4 Nalia Canales Ochoa, BSc,1 Jacqueline Medrano Montero, PhD,1,3
 Estupin
Annelie ~an Rodrı́guez, BSc,1 Marcos Osorio Borjas, MD,5 Mariela Go ngora Marrero, MSc,1
1
Lorenzo Reynaldo Cejas, BSc, Yanetza Gonza lez Zaldivar, BSc, and Dennis Almaguer Gotay, MSc1
1

1
Centre for the Research and Rehabilitation of Hereditary Ataxias, Holguı́n, Cuba
2
Cuban Academy of Sciences, Havana, Cuba
3
School of Physical Culture and Sport, University of Holguı́n, Holguı́n, Cuba
4
Florida Atlantic University, Cellular Neuroscience, Florida, Boca Raton, USA
5
Medical University of Holguı́n, Holguı́n, Cuba

A B S T R A C T : Background: Neurorehabilitation has
become in a widely used approach in spinocerebellar
ataxias, but there are scarce powerful clinical studies
supporting this notion.
Objective: The objective of this study was to assess
the efficacy of a 24-week neurorehabilitative treatment
in spinocerebellar ataxia type 2 patients.
Methods: A total of 38 spinocerebellar ataxia type 2
patients were enrolled in a rater-blinded, 1:1 randomized,
controlled trial using neurorehabilitation for 24 weeks.
The treated group received 6 hours of neurorehabilitation
therapy, emphasizing on balance, coordination, and mus-
cle strengthening on weekdays, whereas the control
group did not receive this intervention. Primary outcome
measure was the Scale for the Assessment and Rating of
Ataxia score, whereas secondary outcome measures
with the controls, mainly for the gait, stance, sitting, fin-
ger chase, and heel-shin test items. Changes in Scale
for the Assessment and Rating of Ataxia scores were
inversely correlated with the mutation size in the reha-
bilitated group. The nonataxia symptom count and sac-
cadic measures were unchanged during the study.
Conclusions: A comprehensive 24-week rehabilitation
program significantly improves the motor cerebellar
symptoms of spinocerebellar ataxia type 2 patients as
assessed by the ataxia rating score likely as result of
the partial preservation of motor learning and neural
plasticity mechanisms. These findings provide evidence
in support of this therapeutic approach as palliative
treatment in spinocerebellar ataxia type 2 suggesting its
use in combination with other symptomatic or neuro-
protective drugs and in prodromal stages. V C 2018 Inter-

included the count of Inventory of Non-Ataxia Symptoms
and saccadic eye movement variables.
Results: The rehabilitated group had high levels of
adherence and retention to the therapy and showed a
significant decrease of Scale for the Assessment and
Rating of Ataxia score at 24 weeks when compared
national Parkinson and Movement Disorder Society
K e y W o r d s : neurorehabilitation; spinocerebellar
ataxia type 2; outcome measure; physical therapy;
neuroplasticity

------------------------------------------------------------ Spinocerebellar ataxias comprise a heterogeneous

zquez-Pe
*Corresponding author: Luis Vela rez, Libertad Street #26, Hol-
guı́n, Cuba, 80100; velazq63@gmail.com
zquez-Pe
Julio Cesar Rodrı́guez-Dı́az and Luis Vela rez are joint first
authors.
Funding agency: Cuban Ministry of Public Health.
Relevant conflicts of interests/financial disclosures: The authors
received funding from the Cuban Ministry of Public Health and disclose
no conflicts in relation to the submitted work.
Received: 26 January 2018; Revised: 28 March 2018;
Accepted: 17 April 2018
Published online 00 Month 2018 in Wiley Online Library
(wileyonlinelibrary.com). DOI: 10.1002/mds.27437
group of neurodegenerative disorders inherited in an
autosomal dominant manner and caused by a degener-
ation of cerebellum and its afferent and efferent con-
nections, spinal cord, peripheral nerves, and brain
stem. Among them, spinocerebellar ataxia type 2
(SCA2) is the second most common disorder, only sur-
passed by SCA3.1 It is caused by an expansion of the
cytosine-adenine-guanine (CAG) tract within the cod-
ing region of the ATXN2 gene, which in turn leads to
an increase in the polyglutamine domain in the hom-
onymous protein.2

Movement Disorders, Vol. 00, No. 00, 2018 1

R O D R IG U E Z - D IA Z E T A L

SCA2 is characterized by a progressive cerebellar syn-

drome accompanied by severe saccadic slowing, periph-
eral neuropathy, autonomic disturbances, pyramidal
signs, cognitive disorders, and sleep disturbances.3 Simi-
lar to other SCAs caused by the polyglutamine domain,
the onset of SCA2 cerebellar syndrome is significantly
controlled by the mutation size2 and is preceded by pro-
dromal manifestations up to more than a decade before
disease onset.4,5
Although SCA2–as with other SCAs–has been studied
extensively, it is still considered an “orphaned treat-
ment” disease, where a cure has not been found.3,6 Nev-
ertheless, a promising gene therapy based on antisense
oligonucleotide approach was significantly efficient in
mouse models,7 and symptomatic therapeutical options
are already available for humans.3,6
Among the therapeutical approaches for SCAs, neuro- FIG. 1. Flow diagram of participants in the clinical trial. [Color figure
rehabilitation is recognized as one of the most useful to can be viewed at wileyonlinelibrary.com]
improve different clinical alterations such as ataxia of
the gait, postural sway, balance, and incoordination of measures were assessed at baseline and 24 weeks in
the upper and lower limbs.8,9 Nevertheless, there are both groups.
few studies assessing the effect of this therapeutic alter-
native on SCAs. Nearly all of these studies included a Participants
small sample size with higher heterogeneity for the dis-
As provided in the Consolidated Standards of
ease duration, ataxia severity, and molecular subtype,9-
13 Reporting Trials (CONSORT) flow diagram (Fig. 1),
excepting 3 studies encompassing relatively large
45 SCA2 patients were assessed for eligibility to par-
cohorts of patients with spinocerebellar degenera-
ticipate in the present study in the Center for the
tions.14-16 Only 2 studies have been performed using a
Research and Rehabilitation of Hereditary Ataxias in
controlled design.13,16 Thus, the heterogeneity in
Holguın (Cuba). The determination of sample size was
patient populations and study designs hampers the
fixed as 45 based on the availability of resources and
unbiased interpretation and comparison of existing
the capability of our rehabilitation unit to conduct
findings.9
this study. To be included, SCA2 had to meet the fol-
In view of the higher prevalence of SCA2 in Cuba as
lowing criteria: clinical and molecular diagnostic of
result of a founder effect,17,18 the larger and homoge-
SCA2 and patient age between 18 and 70 years, irre-
nous population of affected patients provides a good
spective of sex and disease duration. Exclusion criteria
opportunity to evaluate the effect of the rehabilitation
for participation were chronic diseases affecting the
using meaningful designs. That is why the aim of the
nervous system, psychiatric disorders, chronic alcohol
present investigation is to assess the effectiveness of 24-
abuse, pregnancy, and inclusion in any motor training
week neurorehabilitation on the cerebellar and noncere-
program. Of 45 eligible patients, 7 were excluded
bellar features of SCA2 by means a rater-blinded, con-
from the study because 5 did not meet the inclusion
trolled trial encompassing 38 patients.
criteria and 2 individuals declined to participate.
Therefore, after 2 weeks of enrollment, we included
Methods 38 participants. Once selected, 19 SCA2 patients were
randomly assigned to receive physical rehabilitation
Study Design and 19 were allocated to the control group following
This study was a prospective, rater-blinded, con- a simple randomization procedure using sequentially
trolled trial using neurorehabilitation in 38 SCA2 numbered opaque envelopes. To assure proper alloca-
patients who were randomly assigned, in a 1:1 propor- tion concealment, an off-site and uninvolved person
tion, to the rehabilitation group or the control group. sealed each allocation in the envelopes and then gave
The participants allocated to the rehabilitation group the set of sealed envelopes to the enrolling investigator
received 6 hours of neurorehabilitation per day on (L.V.P.).
weekdays during 24 weeks, whereas the patients allo- The main clinical, demographic, and molecular fea-
cated to the control group were asked to continue tures of the enrolled patients are shown in Table 1.
with their daily activities at home or on the job with- No significant difference was found between both
out including any motor training programs. Outcome groups for any of the variables. For the entire sample,

2 Movement Disorders, Vol. 00, No. 00, 2018


TABLE 1. Baseline features of enrolled spinocerebellar ataxia type 2 patients
Variables Rehabilitation group
Gender, f/m 6/13
Age (y) 39.52 6 10.72 (18-63)
Age at onset (y) 28.42 6 9.09 (15-55)
Disease duration (y) 11.10 6 4.01 (3-19)
Expanded alleles (units) 40.15 6 3.80 (32-48)
Nonexpanded alleles (units) 21.84 6 0.50 (20-22)
a
Frequency analysis performed using the v2 test.
b
Mean comparison using the independent t-test.
the age at disease onset was inversely correlated to the
CAG repeat expansion size in the ATXN2 gene
(r 5 20.76; P < .000002).
The study was approved by the Ethics Committee of
the Center for the Research and Rehabilitation of
Hereditary Ataxias (Holguın, Cuba) and was con-
ducted according to the Declaration of Helsinki. Each
patient provided written informed consent for partici-
pation in the study. For ethical reasons, the partici-
pants allocated to the control group received the same
24-week neurorehabilitative treatment once the pre-
sent study was completed.
Rehabilitative Interventions
Rehabilitative interventions were conducted follow-
ing the comprehensive program for neurorehabilitation
of ataxia patients applied in Centro para la investiga-
ciœn y rehabilitacion de ataxias hereditarias (CIRAH)
for more than 15 years. In general, this program com-
prises 1 hour of occupational therapy, 0.5 hours of
motor control for the general conditioning, 4 hours of
physical therapy, and 0.5 hours of psychotherapy per
day on weekdays. The physical therapy was broken
down into 4 sessions (2 in the morning and 2 in the
afternoon) lasting 45 minutes, each followed by 15
minutes of break and hydration. Physical interventions
included range-of-motion exercise for the trunk and
limbs, dynamic and static balance exercises, indoor
and outdoor walking, stair climbing up and down,
coordinative tasks of the upper and lower limbs, and
muscle strengthening exercises, among others. Addi-
tional information of the neurorehabilitative interven-
tion is provided in the Supporting Information
Material 1.
The intervention was given by an experienced physi-
cal therapist with graduate and postgraduate training in
physical culture and sport and devoted specialization in
rehabilitation of neurological diseases (J.C.R.D.). Other
specialists in neurorehabilitation participated in the
intervention sessions (A.E.R., M.G.M., and L.R.C.).
The patient’s retention to the neurorehabilitation
treatment was calculated as the percentage of
enrolled participants who completed the program at
24 weeks and were conceptually defined as opposite
N E U R O R E H A B I L I T A T I O N I N S C A 2
Control group P value
9/10 .319a
38.78 6 10.53 (20-58) .832b
29.89 6 10.10 (10-49) .639b
8.89 6 3.81 (2-14) .100b
40.68 6 4.00 (35-50) .680b
22 6 0.00 (22-22) .178b
of treatment dropout.19 The patient’s adherence to
neurorehabilitation was assessed by the ratio of atten-
dance (calculated by dividing the number of sessions
attended by the number of scheduled sessions)20 and
the index of patient’s adherence behavior (calculated
by dividing the number of sessions with successful ful-
fillment of the intervention program by the number of
attended sessions).
Outcome Measures
Examiners blinded to the experimental group assign-
ment performed all outcome measures. The primary
outcome measure was the Scale for the Assessment and
Rating of Ataxia (SARA),21 whereas the secondary out-
come measures involved the Inventory of Non-Ataxia
Symptoms (INAS) score22 as well as 3 electronystagmo-
graphical measures of saccade eye movements (saccade
velocity, saccade accuracy, and saccade latency).23
The SARA scale is a reliable and validated clinical scale
measuring the severity of ataxia. It comprises 8 items
assessing the gait, posture, speech, and limb kinetic func-
tions and yields a total score of 0 (no ataxia) to 40 (most
severe ataxia).21 The INAS scale determines the extracere-
bellar features of ataxia patients, and its count (0 to 16)
denotes the number of nonataxia symptoms.22
Horizontal saccades were recorded binocularly with a
2-channel electrooculography device (Jaeger-Toennies,
Hoechberg, Germany) using silver chloride electrodes
(Ag-AgCl) over the right and left outer canthus of the
eyes. The electrooculography signal was amplified and
bandpass filtered (0.2-70 Hz). The data were sampled at
a frequency of 200 Hz with a time base of 1000 ms/divi-
sion, sensitivity of 200 mV/division, and a time constant
of 8 seconds.23
The participants were asked to fixate the target in the
central position and to redirect their gaze to the new
location of the target as soon as it appeared in the
periphery and later back in the central position. A total
of 10 centrifugal saccades in both horizontal directions
were registered at 60 8 predictable amplitudes of stimu-
lus. Electrooculography signals were calibrated for a
horizontal angle of 30 8. Saccade latency and accuracy
and maximal saccade velocity were analyzed.23
Movement Disorders, Vol. 00, No. 00, 2018 3
R O D R IG U E Z - D IA Z E T A L
Molecular Analysis
Polymerase chain reaction (PCR) amplification was
used to assess the CAG-triplet repeats in each patient.
Aliquots from the PCR result were sized by fragments
and later analyzed by an ALF Express II apparatus
(Amersham Biosciences, Sweden).
Statistical Analysis
For descriptive statistics of continuous variables,
means and standard deviations were calculated and
categorical variables were expressed as proportions.
The normality of variables was evaluated by the
Kolmogorov-Smirnov test. Comparisons between the
rehabilitation and control groups (between-subjects
comparison) as well as between baseline and 24-week
assessments (within-subjects comparison) were assessed
by repeated-measure analyses of variance (rmANOVA)
using each outcome measure as dependent variables and
the experimental group as the categorical predictor. To
fully understand group differences in the rmANOVA,
we conducted the post-hoc Tukey’s honest significance
difference test. The effect sizes for all outcome measure
in each group were calculated as the standardized
response mean (SRM), which consisted in the mean
score change/standard deviation of score change. SRM
cut-off points of 0.20, 0.50, and 0.80 defined the small,
moderate, and large changes, respectively. SRM values
below 0.20 indicated negligible effect sizes.24 The
improvement of the frequency of 2 groups was com-
pared using the v2 test. Correlation analyses were per-
formed using the Pearson product moment correlation
test. To indicate statistical significance, a level of
P < .05 was used. All analyses were conducted using
Statistica software package version 6 (StatSoft, Inc.
Tulsa, Oklahoma, USA; www.statsoft.com). All analy-
ses were conducted with the commercially available Sta-
tistica software package (StatSoft, Inc.).
Results
The intervention was well tolerated by all rehabili-
tated patients. The retention rate was 100% as no treat-
ment dropouts were observed. Only 4 cases (21%)
reported slight side effects during the intervention, con-
sisting of evoked painful muscle cramps. Regarding the
adherence to the program, we obtained a mean ratio of
attendance of 97.5% (SD 1.96), and all cases attended
to the program for at least 95% of appointments. In
addition, the index of patient’s adherence behavior was
98.28% (SD 2.19). The intervention delivery was ful-
filled as planned in the program.
The rmANOVA disclosed a significant rehabilitation
effect for total score of SARA, with post-hoc compari-
sons showing differences of baseline and final evalua-
tion only in the rehabilitated patients. In addition, no
significant group effect was found either at the baseline
4 Movement Disorders, Vol. 00, No. 00, 2018
FIG. 2. Effects of 24-week neurorehabilitation on motor cerebellar fea-
tures of spinocerebellar ataxia type 2 patients. A: The repeated-
measure analyses of variance of the Scale for the Assessment and
Rating of Ataxia (SARA) total score baseline for the rehabilitated and
control groups. B: Mean comparisons of SARA score items at baseline
and 24 weeks in the rehabilitated group. ns, nonsignificant. [Color fig-
ure can be viewed at wileyonlinelibrary.com]
or 24-week assessments. Accordingly, the rmANOVA
showed a significant effect of the group 3 rehabili-
tation interaction on the SARA score variability, dem-
onstrating the efficacy of this intervention on cerebellar
signs (Fig. 2a). The SRM of the SARA score was 0.78
and 0.12 for the rehabilitated and control groups,
respectively, supporting the rmANOVA findings. The
SARA score changes can be interpreted as large in the
rehabilitated group and negligible in the control group.
The individual SARA scores of all enrolled patients are
shown in Supporting Information Material 2.
Moreover, mean comparisons between baseline and
24-week measures of SARA subscores within the reha-
bilitation group disclosed significant decreases for gait,
stance, sitting, finger chase, and the heel-shin test (Fig.
2b). The rmANOVAS for INAS count and saccadic var-
iables disclosed no significant effects of rehabilitation,
group, or group 3 rehabilitation interaction (Table 2).
In addition, the SRM reached criterion for small in the
INAS count for the control group (0.26), in the saccade
latency for both groups (rehabilitated, 0.32; control,
0.31), and in the saccade accuracy for the control group
(20.32). The remaining SRMs were negligible.
Correlation analyses disclosed significant correlations
between the delta SARA score (DSARA 5 SARAbaseline 2
SARA24-week) with the expanded CAG repeats (r 5 20.48;
P 5 .036) and age at onset (r 5 0.47; P 5 .040). However,
this measure showed no correlation with age (r 5 20.39;
P 5 .095), disease duration (r 5 20.02; P 5 .929), ratio of
attendance (r 5 0.42; P 5 .070), or index of the patient’s
adherence behavior (r 5 0.02; P 5 .933).

TABLE 2. The rmANOVAs of Inventory of Non-Ataxia Symptoms (INAS) count and saccade measures during the rehabilita-
tive treatment
Rehabilitation group
Variables Baseline 24 weeks
INAS count 3.68 6 0.21 3.74 6 0.20
(3.3-4.1) (3.4-4.1)
Saccade velocity, 8/secs 210.11 6 28.73 193.68 6 20.92
(151.8-268.4) (151.1-236.4)
Saccade latency, ms 283.07 6 18.17 263.02 6 17.00
(242.4-314.4) (229.3-295.5)
Saccade accuracy, % 85.26 6 4.06 86.31 6 3.90
(78.9-95.8) (79.4-94.8)
Mean 6 standard error of the mean are provided. Data within parenthesis are the 95% confidence intervals. rmANOVAs, repeated-measure analyses of
variance.
a
Group 3 Rehabilitation effects.
Discussion
This article describes the first controlled trial of neuro-
rehabilitation in SCA2 patients. Throughout this study,
we demonstrated the high retention and adherence to a
24-week program of comprehensive rehabilitation and
its efficacy on the cerebellar signs, but not on nonataxia
symptoms and saccade abnormalities.
As compared to other physiotherapy and rehabilita-
tion programs, the adherence and retention levels of
the present study are certainly higher than other phys-
iotherapy and rehabilitation programs,25-28 which is a
result of the high patient efficacy expectancy and
motivation because of the positive impacts of this 15-
year program applied in more than 600 patients with
ataxia.
The improvement of cerebellar signs was demon-
strated by the significant reduction of the mean SARA
score in the rehabilitated group. Among the available
ataxia’s rating scale, the SARA score utilizes the most
impactful properties, taking into consideration the
semiquantitative measure of cerebellar signs; therefore,
it has a higher application in clinical trials.29 The
analysis of the SARA scale features gives us insight
about the response of cerebellar function through the
physical exercises in the rehabilitating group. The find-
ings identified the ataxic gait and postural instability
as well as upper and lower limb dysmetria as the
abnormalities that showed the best responses in
the experimental group. A significant reduction of the
SARA score after neurorehabilitative therapy was pre-
viously observed by Miyai and colleagues16 in 42
patients with pure cerebellar degenerations (including
20 cases with SCA6 and 6 with SCA31) after a shorter
treatment period than our study (4 weeks). Although
we did not obtain SARA scores at the 4-week period
of rehabilitation, the faster treatment effects in the
study by Miyai et al. could be expected as a result of
the less progressive nature of pure cerebellar ataxia
when compared with SCA2 patients.30
N E U R O R E H A B I L I T A T I O N I N S C A 2
Control group
Baseline 24 weeks rmANOVA findingsa
3.63 6 0.21 3.79 6 0.20 F(1.36) 5 0.33;
(3.2-4.1) (3.4-4.2) P 5 .569
155.64 6 27.96 173.20 6 20.36 F(1.36) 5 1.11;
(98.9-212.4) (131.8-214.5) P 5 .300
308.51 6 17.69 273.87 6 16.55 F(1.36) 5 0.40;
(272.5-344.5) (240.8-306.9) P 5 .531
82.57 6 3.96 84.38 6 3.79 F(1.36) 5 0.40;
(74.1-91.0) (76.7-92.1) P 5 .530
The improvement of cerebellar signs as a result of the
neurorehabilitation suggests the partial preservation of
motor learning and neural plasticity mechanisms in the
cerebellum of SCA2 patients. For several years, many
researchers have offered convincing evidence regarding
the neuroplasticity properties of the cerebellar circuitry,
focusing on the synapses level between parallel fibers
and Purkinje cells in the molecular layer of the cerebel-
lar cortex.31,32
Moreover, previous studies performed in human and
animal models have demonstrated the role of physical
exercises as a stimulating factor of neural plasticity by
the increase of brain-derived neurotrophic factor
(BDNF) levels, axonal regeneration, and the promotion
of long-term potentiation (LTP)-like plasticity in the
motor cortex.33-36 Also, physical exercise has been
proven to provide beneficial effects in the cerebellar
mitochondrial bioenergetics systems of rats,37 and this
could be used as a model for a therapeutic approach for
SCA2 patients in which the bioenergetic deficits caused
by the ataxin-2 mutation38-40 could be alleviated.
Of note, rehabilitating patients carrying the shorter
expanded CAG repeats and a higher age at onset
exhibited the higher reductions of SARA score at the
end of the treatment. This finding identified the muta-
tion size as an important determinant for the thera-
peutic responses of neurorehabilitation. These findings
demonstrate the importance of this molecular parame-
ter on SCA2 patients’ cerebellar function, specifically
on the mechanisms of neuronal plasticity. In fact, a
significant relationship between the expanded ATXN2
alleles and the inositol-3-phosphate receptor has been
observed in Purkinje cells cultures from a Spinocere-
bellar Ataxia type 2 transgenic model carrying 58 glu-
tamines in the ataxin-2 protein (SCA2-58Q)
transgenic mouse,41 which suggests the disruption of
calcium-related neural plasticity mechanisms and
seems to explain the disease onset.42
The nonsignificant response of the nonataxia symp-
toms assessed by the INAS count could be explained
Movement Disorders, Vol. 00, No. 00, 2018 5
R O D R IG U E Z - D IA Z E T A L
by the rationale focus of our neurorehabilitative inter-
vention, which was mainly based on physical exercises
stimulating motor cerebellar functions and the short
time of treatment. These same explanations could jus-
tify the lack of significant changes of saccade abnor-
malities after the rehabilitation, together with the
complicated physiopathological underpinnings of these
features involving severely atrophied areas beyond the
cerebellum, such as the pons, brain cortex, and basal
ganglia.43 In a previous open-label trial enrolling 96
SCA2 patients for 6 months, we found a significant
effect of neurorehabilitative therapy on the saccade
latency,14 but its contradiction with the present find-
ings can be explained by the larger sample size and
intervention time of the study.
Limitations of the present study include the lack of
objective assessments of motor improvements after the
treatment, such as biomechanical analyses, posturogra-
phy, portable electromyography, or wearable sensors.
Our study showed no data regarding the posttreatment
follow-up of the rehabilitated patients, hindering our
understanding about the duration of the therapy effects.
Therefore, future research should be focused on the
usage of more objective outcome measures to assess the
motor improvements alongside the study of physiologi-
cal, biochemical, and molecular biomarkers of neuro-
plastic changes elicited by neurorehabilitation.
The high retention and adherence levels of the present
rehabilitation program alongside its efficacy to improve
motor cerebellar manifestations support the feasibility
of this intervention in a large population with slight to
moderate SCA2 or other related SCAs. In addition, our
findings suggest the need for further neurorehabilitation
approaches in other disease statuses, such as the prodro-
mal stage and advanced disease, and raise the need for
the cost analysis of neurorehabilitation.
In summary, this article provides important clinical
messages about the effectiveness of neurorehabilitation
in SCA2 patients demonstrating the efficacy of a 24-
week rehabilitative therapy on specific motor cerebellar
manifestations such as gait, posture, and limb incoordi-
nation. In addition, this neurorehabilitative treatment
could be combined with other symptomatic pharmaco-
logical alternatives to potentiate their effects on other
motor and nonmotor disease features, and ultimately
this could be used as preventive treatment during pro-
dromal stages. From a physiopathological view, our
findings provide evidence regarding the partial preserva-
tion of motor learning and neural plasticity mechanisms
in light to moderate SCA2, regardless of the early toxic
effect of the polyglutamine domain expansion.
Acknowledgments: We express our gratitude to all SCA2 patients
enrolled in this study, as well as to the Cuban Ministry of Public Health
for their cooperation.
6 Movement Disorders, Vol. 00, No. 00, 2018
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Supporting Data
Additional Supporting Information may be found in
the online version of this article at the publisher’s
website.
Movement Disorders, Vol. 00, No. 00, 2018 7